Efficacy and Safety Study of MCI-196 Versus Simvastatin for Dyslipidaemia in Chronic Kidney Disease (CKD) Subjects on Dialysis

A Phase III, Multicentre, Double-blind, Double-dummy, Randomised, Flexible-dose, Comparative Study of MCI-196 Versus Simvastatin for the Treatment of Dyslipidaemia in Subjects With Chronic Kidney Disease on Dialysis (Incorporating a Placebo-controlled Withdrawal Phase)

The primary objective of this study is to demonstrate the superiority of MCI-196 over placebo and non-inferiority with simvastatin in reducing serum low-density lipoprotein (LDL)-cholesterol in subjects with chronic kidney disease Stage V on dialysis. This study incorporates a Washout Period and two treatment periods - an active comparison phase and a placebo-controlled withdrawal phase.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: MCI-196; Drug: Placebo of Simvastatin; Drug: Placebo of MCI-196; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus
  • Gomel, Belarus
  • Grodno, Belarus
  • Minsk, Belarus
  • Vitebsk, Belarus
• Bulgaria
  • Gabrovo, Bulgaria
  • Plovdiv, Bulgaria
  • Sofia, Bulgaria
• Croatia
  • Karlovac, Croatia
  • Osijek, Croatia
• Denmark
  • Esbjerg, Denmark
  • Roskilde, Denmark
• Indonesia
  • Jakarta, Indonesia
  • Malang, Indonesia
  • Medan, Indonesia
  • Palembang, Indonesia
  • Tamanlarea Makassar, Indonesia
• Israel
  • Ashkelon, Israel
  • Nahariya, Israel
• Italy
  • Bellano, Italy
  • Catania, Italy
  • Lecco, Italy
  • Merate, Italy
  • Milano, Italy
  • Oggiono, Italy
• Latvia
  • Riga, Latvia
  • Valmiera, Latvia
• Lithuania
  • Kaunas, Lithuania
  • Kedauniai, Lithuania
  • Vilnius, Lithuania
• Malaysia
  • Johor, Malaysia
  • Kelantan, Malaysia
  • Penang, Malaysia
  • Perak, Malaysia
• Romania
  • Bucharest, Romania
  • Timisoara, Romania
• Singapore
  • Singapore, Singapore
• Thailand
  • Bangkok, Thailand
  • Phitsanulok, Thailand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, and is >=18 years old
• Stable hemodialysis or peritoneal dialysis
• Subjects undergoing regular dialysis treatment
• If Female and of child-bearing potential, have a negative serum pregnancy test
• Male subjects must agree to use appropriate contraception

Exclusion Criteria:

• Current clinically significant medical comorbidities, which may substantially compromise subject safety, or expose him/her to undue risk, or interfere significantly with study procedures and which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study
• Serum albumin level < 30 g/L
• Triglycerides level > 6.76 mmol/L (600 mg/dL)
• LDL-cholesterol level > 4.94 mmol/L (190 mg/dL)
• A History of significant gastrointestinal motility problems
• Biliary obstruction or proven liver dysfunction
• A positive test for HIV 1 and 2 antibodies
• A history of substance or alcohol abuse within the last year
• The subject has a history of rhabdomyolysis or myopathy
• Schedule to receive a kidney transplant within the next 6 months
• The subject has porphyria
• Participation in a clinical study with any experimental medication in the last 30 days or an experimental biological product within the last 90 days prior to signing of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 MCI-196	Drug: MCI-196; Tablets of 3 g to 12 g/day (3 times a day) with dose escalation design during 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20); Other Names: Colestilan(INN); Colestimide(JAN); CHOLEBINE®; BindRen®; Drug: Placebo of Simvastatin; Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
Placebo Comparator: 2 Placebo of MCI-196	Drug: Placebo of Simvastatin; Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20); Drug: Placebo of MCI-196; Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
Active Comparator: 3 Simvastatin	Drug: Placebo of MCI-196; Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20); Drug: Simvastatin; Tablets of 10 mg to 40 mg/day (once a day) with dose escalation design during 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
Placebo Comparator: 4 Placebo of Simvastatin	Drug: Placebo of Simvastatin; Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20); Drug: Placebo of MCI-196; Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2)	Percent Change from Week 16 to Week 20 (LOCF)	week20 minus week16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Serum LDL-cholesterol Levels From Baseline to Week 16 (LOCF) (ITT1)	Percent Change from Baseline to Week 16 (LOCF)	week16 minus week0
Change in Phosphorus(P), Calcium(Ca), Calcium-phosphorus Ion Product(PxCa) and Parathyroid Hormone (PTH)		16 weeks and 20 weeks
Vital Signs, Adverse Events, and Laboratory Values		throughout study

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 9, 2009
• First Posted (Estimate): March 10, 2009

Study Record Updates

• Last Update Posted (Estimate): December 30, 2014
• Last Update Submitted That Met QC Criteria: December 8, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Dyslipidemia; Chronic Kidney Disease; Dialysis; Bile acid sequestrant
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Lipid Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Gastrointestinal Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Bile Acids and Salts
• Other Study ID Numbers: MCI-196-E11